Microvascular transport is a critical cardiovascular function. If nutrient delivery or blood-tissue exchange and fluid balance are compromised, organ function is impaired. The heart is particularly vulnerable to alterations in normal microvascular function. The fluid transported through the microcirculation, contains salts, hormones, proteins, and formed elements. We recently reported that an interaction exists between blood proteins, blood cells, and the coronary microcirculation. Coronary permeability to macromolecules is reduced when blood cells and/or protein are included in the perfusate. This finding has applied implications in design of cardioplegia solutions, to protect the heart during cardiac surgery, and solutions for preserving transplantable organs such as liver, kidneys, and the heart. Other workers suggest that protein and platelets are required to maintain normal microvascular integrity, but these concepts have not been rigorously tested in mammalian microcirculations. The aims of this project are to further our understanding of the effects of blood proteins, red cells, platelets, and leukocytes on microvascular integrity in the heart and skeltal muscle. We will dtermine which blood cell types influence permeability and how much are required to do so. We will determine if the deleterious effects of protein-free and cell-free perfusion can be reversed by replacement and, how long it takes. Related studies include an examination of the effects of platelet release products, serotonin, and histamine on coronary and muscle mucrovascular permieability. Studies of bradykinin and certain prostaglandins which are both known to increase during cardiopulmonary bypass are proposed. In related cardioplegia studies, we will determine if preservation of coronary microvascular integrity contributes to the superior protective effects of cold blood cardioplegia. Studies on cardiac preservation will examine the relationship between microvascular function and cardiac contractile function. We will employ direct visualization techniques to simultaneously view the effects of blood components on microvascular permeability and perfusion. Furthermore, parallel radiotracer uptake studies will measure whole organ macromolecule exchange and distribution volumes. These studies will extend our current knowledge of the interaction of blood components with blood vessels and suggest improved solutions for cardiac protection and organ preservation.